Temozolomide (TMZ), an anti-tumor drug, has broad-spectrum bioactivity of anti-tumor in the murine tumor model. Clinical studies show that TMZ possesses the activities on malignant melanoma, mycosis fungoides, and advanced glioma. In addition, it also displays a subcutaneously therapeutic effect on xenotransplantated brain tumor and lung tumor in mice. In vitro anti-tumor trials prove that TMZ has anti-tumor activity against a broad range of tumor types, including brain tumor, ovarian tumor, melanoma, and those resistant to chemotherapy using conventional drugs, such as dacarbazine, carmustine, cisplatin, doxorubicin, 5-fluorouracil, etoposide, and vinblastine.
The pharmacokinetics study in mouse model showed that, after being administered, TMZ was absorbed rapidly in vivo with a half-life time of 1.13 h (i.p.) or 1.29(p.o.). In phase I clinical trial of TMZ, it was found that it was absorbed very rapidly, reaching maximum plasma concentration within 0.7 hour and having a half-life time of 1.8 h. Also, it demonstrated good distribution to all tissues, including penetration into the blood brain barrier via kidney, lung, and liver (Brindley et al., 1986; Newland et al., 1997). But, the plasma concentration of temozolomide declines very quickly after the administration of the drug. Therefore repeated administrations are required to keep the effective drug concentration in blood, and thus bring patients with both inconvenience and agonies.
Controlled release of drug is able to release the drug at a relatively constant rate during a certain period of time. The controlled release system may be exemplified by the biodegradable implantable tablet and the non-biodegradable implantable tablet, both of which have been used for the controlled release of some drugs. However, the controlled release system for TMZ has not been reported until now.